An insight into the discovery, clinical studies, compositions, and patents of macozinone: A drug targeting the DprE1 enzyme of Mycobacterium tuberculosis

Mohd Imran; Shah Alam Khan; Syed Mohammed Basheeruddin Asdaq; Mazen Almehmadi; Osama Abdulaziz; Mehnaz Kamal; Mohammed Kanan Alshammari; Lojain Ibrahim Alsubaihi; Khansa Hamza Hussain; Abrar Saleh Alharbi; A Khuzaim Alzahrani

doi:10.1016/j.jiph.2022.08.016

An insight into the discovery, clinical studies, compositions, and patents of macozinone: A drug targeting the DprE1 enzyme of Mycobacterium tuberculosis

J Infect Public Health. 2022 Oct;15(10):1097-1107. doi: 10.1016/j.jiph.2022.08.016. Epub 2022 Sep 1.

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia. Electronic address: mohammad.baks@nbu.edu.sa.
² Department of Pharmaceutical Chemistry, College of Pharmacy, National University of Science and Technology, Muscat, Oman. Electronic address: shahalam@nu.edu.om.
³ Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, 13713 Riyadh, Saudi Arabia. Electronic address: sasdag@mcst.edu.sa.
⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. Electronic address: Mazenn@tu.edu.sa.
⁵ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. Electronic address: O.osama@tu.edu.sa.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia. Electronic address: m.uddin@psau.edu.sa.
⁷ Department of Pharmaceutical Care, Rafha Central Hospital, North Zone, Rafha 76321, Saudi Arabia. Electronic address: ii_kanan101@outlook.com.
⁸ Department of Pharmaceutical Care, Prince Sultan Armed Forces Hospital, Medina 42313, Saudi Arabia. Electronic address: Lojainalsubaihi@gmail.com.
⁹ Department of Cardiac Science, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: Khansa.hussain82@gmail.com.
¹⁰ Department of Pharmaceutical Sciences, Primary Healthcare Center, West Zone, Mecca 24341, Saudi Arabia. Electronic address: aalharbi384@moh.gov.sa.
¹¹ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia. Electronic address: akaalz@nbu.edu.sa.

PMID: 36122509
DOI: 10.1016/j.jiph.2022.08.016

Abstract

Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1) inhibitors are an innovative and futuristic orally active group of antituberculosis agents. A few DprE1 inhibitors are in the clinical trial for tuberculosis (TB), including macozinone. This review highlights the discovery, developmental status, clinical studies, patents, and prospects of macozinone (MCZ). The patent and non-patent literature search was done by entering keywords such as macozinone; MCZ; PBTZ169; PBTZ-169 in Pubmed, Espacenet, Patentscope, and the USPTO databases. However, data on Sci-Finder was searched using CAS registry number: 1377239-83-2. MCZ clinical trial studies were retrieved from the clinicaltrials.gov database using the exact keywords. The chemical structure of MCZ was disclosed in 2009. Accordingly, patents/patent applications published from 2009 to June 12, 2022, have been discussed herein. MCZ and MCZ hydrochloride salt patents were granted in 2014 and 2019, respectively, in the USA. The patent literature and the clinical trial studies suggest capsule, tablet, and suspension formulations of crystalline MCZ and its hydrochloride salt as the possible and prospective dosage forms to treat TB. Some combinations of MCZ with other drugs (chloroquine, telacebec, tafenoquine, TBI-166, and sanfetrinem) with improved anti-TB efficacy have been documented. Based on the literature covered in this review article on the clinical studies and patents applied/granted to MCZ, it can be inferred that MCZ seems to be a promising DprE1 inhibitor and could help to tackle the emerging dilemma of drug-resistant either as a monotherapy or in combination with additional anti-TB agents. Furthermore, the authors anticipate the development of new combinations, salts, and polymorphs of MCZ as anti-TB agents shortly. This review article might prove beneficial to the scientific community as it summarizes chemistry, pharmacology and provides an update on the clinical studies and patents/patent applications of one of the emerging anti-TB drugs in one place.

Keywords: DprE1; Macozinone; PBTZ169; Patent; Tuberculosis.

Publication types

Review

MeSH terms

Antitubercular Agents / pharmacology
Antitubercular Agents / therapeutic use
Drug Delivery Systems
Humans
Mycobacterium tuberculosis*
Prospective Studies
Tuberculosis* / drug therapy
Tuberculosis* / microbiology

Substances

macozinone
Antitubercular Agents